PIO2STOP: Second STOP After Pioglitazone Priming in CML Patients
Study Details
Study Description
Brief Summary
Single-center study, prospective, phase II trial.
The study objectives are :
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To assess safety and pharmacokinetics of the combination of PIO and TKI in CML subjects who experience a loss of MMR following a first TKI discontinuation.
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To assess survival without loss of MMR over a 12 months period following a second TKI discontinuation in subjects who achieve or maintain < MR4.5 with the combination PIO and TKI administered for at least 6 months.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: CML patients following molecular response loss
|
Drug: Pioglitazone + TKI
|
Outcome Measures
Primary Outcome Measures
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [Up to 24 months after inclusion]
- Treatment free survival after pioglitazone and tyrosine kinase inhibitor discontinuation. [Up to 24 months after inclusion]
Eligibility Criteria
Criteria
Inclusion Criteria:
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CML in any phase. patient in MR4
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Loss of MMR following a first or subsequent TKI discontinuation trial.
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Patient prior treated with imatinib, dasatinib, nilotinib, or bosutinib
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Age >18 years.
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Serum bilirubin <1.5 x upper limit of normal values.
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AST (SGOT)/ALT (SGPT) <2.5x upper limit of normal values.
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Females of child bearing potential must agree to abstain from sexual activity or to use a medically approved contraceptive measure/regimen during and for 3 months after the treatment period. Women of child bearing potential must have a negative urine pregnancy test at the time of enrollment. Acceptable methods of birth control include oral contraceptive, intrauterine device, transdermal/implanted or injected contraceptives and abstinence.
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Males must agree to abstain from sexual activity or agree to utilize a medically-approved contraception method during and for 3 months after the treatment period.
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Signed informed consent.
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Be able and willing to comply with study visits and procedures
Exclusion Criteria:
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Known loss of CCyR by marrow cytogenetic or blood FISH for BCR-ABL1.
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Loss of CHR.
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Participation in another clinical trial with any investigative drug within 30 days prior to study enrolment.
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Prior allogeneic hematopoietic stem cell transplantation.
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Patient requiring anti-diabetic medications to manage hyperglycemia.
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Cardiovascular disease: history of congestive heart failure, myocardial infarction within the 6 months of study entry, symptomatic cardiac arrhythmia requiring treatment.
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Hepatic insufficiency
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History of bladder cancer.
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Diagnosed hematuria.
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Known osteoporosis with curative therapy (prophylactic therapy is not an exclusion criteria)
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Known history of macular edema.
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Known history of ABL1-domain mutation associated with resistance to the discontinued TKI.
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Known allergy to PIO.
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Pregnant or breastfeeding.
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Use of TZD within 28 days prior to enrollment.
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Significant gastrointestinal condition that could potentially impair the absorption or disposition of the drug.
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Uncontrolled peripheral edema (2+ or more) of any etiology
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Centre Hospitalier de Versailles | Le Chesnay | France | 78150 | |
| 2 | Hôpital Bicêtre | Le Kremlin-Bicêtre | France | 94275 | |
| 3 | CHU de Nantes | Nantes | France | 44093 | |
| 4 | CHU de Rennes | Rennes | France | 35033 |
Sponsors and Collaborators
- Versailles Hospital
- Pr Philippe ROUSSELOT
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- P16/05_PIO2STOP